High-Throughput Assay and Discovery of Small Molecules that Interrupt Malaria Transmission.

Cell Host Microbe
Authors
Keywords
Abstract

Preventing transmission is an important element of malaria control. However, most of the current available methods to assay for malaria transmission blocking are relatively low throughput and cannot be applied to large chemical libraries. We have developed a high-throughput and cost-effective assay, the Saponin-lysis Sexual Stage Assay (SaLSSA), for identifying small molecules with transmission-blocking capacity. SaLSSA analysis of 13,983 unique compounds uncovered that >90% of well-characterized antimalarials, including endoperoxides and 4-aminoquinolines, as well as compounds active against asexual blood stages, lost most of their killing activity when parasites developed into metabolically quiescent stage V gametocytes. On the other hand, we identified compounds with consistent low nanomolar transmission-blocking activity, some of which showed cross-reactivity against asexual blood and liver stages. The data clearly emphasize substantial physiological differences between sexual and asexual parasites and provide a tool and starting points for the discovery and development of transmission-blocking drugs.

Year of Publication
2016
Journal
Cell Host Microbe
Volume
19
Issue
1
Pages
114-26
Date Published
2016 Jan 13
ISSN
1934-6069
DOI
10.1016/j.chom.2015.12.001
PubMed ID
26749441
PubMed Central ID
PMC4723716
Links
Grant list
R01 AI090141 / AI / NIAID NIH HHS / United States
R01 AI103058 / AI / NIAID NIH HHS / United States
R01AI090141 / AI / NIAID NIH HHS / United States
R01AI103058 / AI / NIAID NIH HHS / United States